scholarly journals Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells

Blood ◽  
1991 ◽  
Vol 77 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
HE Broxmeyer ◽  
S Cooper ◽  
L Lu ◽  
G Hangoc ◽  
D Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hla Dr ◽  
Mast Cell Growth Factor

Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte- macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

scholarly journals Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells

Blood ◽  
1991 ◽  
Vol 77 (10) ◽  
pp. 2142-2149 ◽  
Author(s):  
HE Broxmeyer ◽  
S Cooper ◽  
L Lu ◽  
G Hangoc ◽  
D Anderson ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Colony Formation ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hla Dr ◽  
Mast Cell Growth Factor

Abstract Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte- macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.

scholarly journals Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2216-2221 ◽  
Author(s):  
CE Carow ◽  
G Hangoc ◽  
SH Cooper ◽  
DE Williams ◽  
HE Broxmeyer
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Cord Blood ◽  
Primary Cultures ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Factor C ◽  
Mast Cell Growth Factor

Abstract The replating capability of human multipotential (colony-forming unit- granulocyte-erythrocyte-macrophage-megakaryocyte [CFU-GEMM]) and erythroid (burst-forming unit-erythroid [BFU-E]) progenitors was assessed in vitro as a potential measure of self-renewal using purified, recombinant (r) human (hu) or murine (mu) mast cell growth factor (MGF), a ligand for the c-kit proto-oncogene receptor. Primary cultures of human umbilical cord blood or adult human bone marrow cells were initiated in methylcellulose with erythropoietin (Epo) alone or in combination with rhu interleukin-3 (IL-3) or MGF. Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed from primary cultures and reseeded into secondary methylcellulose cultures containing a combination of Epo, MGF, and rhu granulocyte-macrophage colony- stimulating factor (GM-CSF). The data showed a high replating efficiency of cord blood and bone marrow CFU-GEMM in response to Epo + MGF in terms of the percentage of colonies that could be replated and the number of secondary colonies formed per replated primary colony. The average number of hematopoietic colonies and clusters apparent from replated cultures of cord blood or bone marrow CFU-GEMM stimulated by Epo + MGF was greater than with Epo + rhuIL-3 or Epo alone. Replated cord blood CFU-GEMM gave rise to CFU-GEMM, BFU-E, and GM colony-forming units (CFU-GM) in secondary cultures. Replated bone marrow CFU-GEMM gave rise mainly to CFU-GM in secondary cultures. A more limited capacity for replating of cord blood and bone marrow BFU-E was observed. These studies show that CFU-GEMM responding to MGF have an enhanced replating potential, which may be promoted by MGF. These studies also support the concept that MGF acts on more primitive progenitors than IL-3.

scholarly journals Long-term generation and expansion of human primitive hematopoietic progenitor cells in vitro

Blood ◽  
1993 ◽  
Vol 81 (3) ◽  
pp. 661-669 ◽  
Author(s):  
EF Srour ◽  
JE Brandt ◽  
RA Briddell ◽  
S Grigsby ◽  
T Leemhuis ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Bone Marrow Cells ◽  
Fold Increase ◽  
Hematopoietic Progenitor Cells ◽  
Proliferative Potential ◽  
Hematopoietic Progenitor ◽  
Hla Dr

Abstract Although sustained production of committed human hematopoietic progenitor cells in long-term bone marrow cultures (LTBMC) is well documented, evidence for the generation and expansion of human primitive hematopoietic progenitor cells (PHPC) in such cultures is lacking. For that purpose, we attempted to determine if the human high proliferative potential colony-forming cell (HPP-CFC), a primitive hematopoietic marrow progenitor cell, is capable of generation and expansion in vitro. To that effect, stromal cell-free LTBMC were initiated with CD34+ HLA-DR-CD15- rhodamine 123dull bone marrow cells and were maintained with repeated addition of c-kit ligand and a synthetic interleukin-3/granulocyte-macrophage colony-stimulating factor fusion protein. By day 21 of LTBMC, a greater than twofold increase in the number of assayable HPP-CFC was detected. Furthermore, the production of HPP-CFC in LTBMC continued for up to 4 weeks, resulting in a 5.5-fold increase in HPP-CFC numbers. Weekly phenotypic analyses of cells harvested from LTBMC showed that the number of CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 CD34+ HLA-DR- cells increased from 10(4) on day 0 to 56 x 10(4) by day 21. To examine further the nature of the in vitro HPP-CFC expansion, individual HPP- CFC colonies were serially cloned. Secondary cloning of individual, day 28 primary HPP-CFC indicated that 46% of these colonies formed an average of nine secondary colony-forming unit--granulocyte-macrophage (CFU-GM)--derived colonies, whereas 43% of primary HPP-CFC gave rise to between one and six secondary HPP-CFC colonies and 6 to 26 CFU-GM. These data show that CD34+ HLA-DR- CD15- rhodamine 123dull cells represent a fraction of human bone marrow highly enriched for HPP-CFC and that based on their regeneration and proliferative capacities, a hierarchy of HPP-CFC exists. Furthermore, these studies indicate that in the presence of appropriate cytokine stimulation, it is possible to expand the number of PHPC in vitro.

scholarly journals Interleukin 6 is a permissive factor for monocytic colony formation by human hematopoietic progenitor cells.

1992 ◽  
Vol 175 (4) ◽  
pp. 1151-1154 ◽  
Author(s):  
J H Jansen ◽  
J C Kluin-Nelemans ◽  
J Van Damme ◽  
G J Wientjens ◽  
R Willemze ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Progenitor Cells ◽  
Interleukin 6 ◽  
Colony Formation ◽  
Bone Marrow Cells ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Gm Csf ◽  
Marrow Cells

Since monocytes and macrophages that arise during the culture of bone marrow progenitor cells are potential sources of interleukin 6 (IL-6), we investigated whether auto- or paracrine production of this factor is involved in colony formation by normal hematopoietic progenitor cells. We added a polyclonal anti-IL-6 antiserum and a monoclonal anti-IL-6 antibody to cultures of monocyte- and T cell-depleted bone marrow cells. Colony formation was stimulated with granulocyte/monocyte-colony-stimulating factor (GM-CSF), monocyte-CSF, or IL-3. Addition of anti-IL-6 antibody resulted in decreased numbers of monocytic colonies to 40-50% of control values, whereas the numbers of granulocytic colonies were not altered. The inhibitory effect was preserved in cultures of CD34(+)-enriched bone marrow cells. As a second approach, we added a monoclonal antibody directed against the IL-6 receptor to cultures of monocyte- and T cell-depleted bone marrow cells. This antibody almost completely inhibited the growth of monocytic colonies, again without decreasing the number of granulocytic colonies. Finally, the importance of IL-6 in monocytopoiesis was demonstrated in serum-deprived bone marrow cultures: addition of exogenous IL-6 to cultures stimulated with GM-CSF resulted in increased numbers of monocytic colonies. Our results indicate that the permissive presence of IL-6 is required for optimal monocytic colony formation by bone marrow progenitor cells.

scholarly journals The supportive effects of erythropoietin and mast cell growth factor on CD34+/CD36- sorted bone marrow cells of myelodysplasia patients

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 505-510 ◽  
Author(s):  
S Brada ◽  
J de Wolf ◽  
D Hendriks ◽  
M Esselink ◽  
M Ruiters ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Bone Marrow Cells ◽  
Early Stage ◽  
Erythroid Differentiation ◽  
Erythroid Development ◽  
Mast Cell Growth Factor ◽  
Marrow Cells

In the present study, we analyzed the capacity of CD34+/CD36- sorted bone marrow cells of myelodysplasia patients (n = 4) to differentiate along the erythroid lineage in the presence of erythropoietin (Epo) and mast cell growth factor (MGF). Two subgroups could be identified. In 6 patients, a normal number of burst-forming units-erythroid (BFU-Es) were cultured from CD34+/CD36- sorted cells. Cells from these patients did have the capacity to differentiate to colony-forming units- erythroid (CFU-Es) progenitors in cell suspension cultures with Epo plus MGF followed by Epo in the culture assay. Moreover, the cells became CD34-/CD36+/gly-cophorin A (GpA)+ after 7 days of culture with Epo plus MGF, a pattern comparable to that of normal progenitors. In contrast, in 8 patients, a different pattern was observed. No BFU-Es or a low number of BFU-Es were cultured from the CD34+/CD36- sorted cell fraction that was, in most of the cases, incapable of differentiating to CFU-E progenitors. Flow cytometry of the sorted population showed that, after 7 days of culture with Epo plus MGF, a high proportion of CD34+/CD36- cells persisted, whereas a low proportion of cells became CD34-/CD36+/GpA+. The unresponsiveness is not caused by the used growth factor combination, because the addition of interleukin-3 did not correct the defect. Evi-1 expression was studied in 9 cases to show whether an aberrant Evi-1 expression correlates with a disturbed erythroid development. Evi-1 expression was shown in 4 of 9 cases, whereas 3 of 9 cases did have a disturbed erythroid differentiation. In summary, the results show that the defects in the erythroid development in a subpopulation of patients with myelodysplasia is localized at an early stage of the erythroid differentiation and is associated with the persistent expression of the CD34 antigen and, in some cases, with the expression of Evi-1.

scholarly journals Further phenotypic characterization and isolation of human hematopoietic progenitor cells using a monoclonal antibody to the c-kit receptor

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3159-3167 ◽  
Author(s):  
RA Briddell ◽  
VC Broudy ◽  
E Bruno ◽  
JE Brandt ◽  
EF Srour ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cells ◽  
Cloning Efficiency ◽  
Cell Cloning ◽  
Hematopoietic Progenitor ◽  
Kit Ligand ◽  
Hla Dr

A mouse antihuman monoclonal IgG2a antibody, termed stem cell receptor- 1 (SR-1), specific for a determinant of the c-kit ligand receptor (KR), was used as an immunologic probe to analyze KR expression by human bone marrow hematopoietic progenitor cells. Monoclonal antibodies to CD34 and HLA-DR were used in a multicolor staining protocol in conjunction with SR-1 to further define the phenotypes of various classes of hematopoietic progenitor cells. Expression of KR (SR-1+) on hematopoietic progenitor cells identified subpopulations of cells expressing CD34 (CD34+). While one-half of the CD34- and HLA-DR- expressing cells (CD34+ HLA-DR+) expressed the KR (SR-1+), one-third of the CD34+ cells that lacked HLA-DR expression (CD34+ HLA-DR-) were SR- 1+. The CD34+ HLA-DR+ SR-1+ cell population contained the vast majority of the more differentiated progenitor cells, including the colony- forming unit (CFU) granulocyte-macrophage; burst-forming unit- erythrocyte; CFU-granulocyte, erythrocyte, macrophage, megakaryocyte; and the CFU-megakaryocyte. The overall progenitor cell cloning efficiency of this subpopulation was greater than 31%. By contrast, the CD34+ HLA-DR- SR-1+ cell population contained fewer of these more differentiated progenitor cells but exclusively contained the more primitive progenitor cells, the BFU-megakaryocyte, high proliferative potential-colony-forming cell, and long-term bone marrow culture- initiating cell. The overall progenitor cell cloning efficiency of this subpopulation was greater than 7%. Both the CD34+ HLA-DR- and CD34+ HLA- DR+ cell subpopulations lacking KR expression contained few assayable hematopoietic progenitor cells. Long-term bone marrow cultures initiated with CD34+ HLA-DR- SR-1+ but not CD34+ HLA-DR- SR-1- cells, which were repeatedly supplemented with c-kit ligand (KL) and interleukin-3, generated assayable progenitor cells of at least 2 lineages for 10 weeks. These experiments demonstrate the expression of the KR throughout the hierarchy of human hematopoietic progenitor cell development. We conclude from our data that the KL and KR play a pivotal role in cytokine regulation of both the primitive and more differentiated human hematopoietic progenitor cells.

Interferon-gamma Has Dual Potential in Inhibiting or Promoting Survival and Growth of Haematopoietic Progenitors: Interactions with Stromal Cell-Derived Factor-1.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4216-4216
Author(s):  
Deog-Yeon Jo ◽  
Jin-Hee Hwang ◽  
Seong-Woo Kim ◽  
Hwan-Jung Yun ◽  
Samyong Kim
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Progenitor Cells ◽  
Clonal Growth ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cd34 Cells ◽  
Survival And Growth ◽  
Ifn Γ ◽  
Stromal Cell Derived Factor

Abstract Despite many apparently contradictory reports, IFN-γ is well known as a hematopoiesis-inhibitory cytokine and is implicated in the pathogenesis of aplastic anemia. It has been shown that IFN-γ intrinsically and simultaneously induces specific and conflicting signalling pathways and transcriptional programs that contribute to the potential dual effects of IFN-γ in promoting or inhibiting proliferation of murine pro-B cells (Asao et al, J Biol Chem275: 867, 2000). We explored the dual roles of IFN-γ in the inhibition or promotion of the survival and growth of hematopoietic progenitors, especially with regard to interactions with stromal cell-derived factor-1 (SDF-1). IFN-γ partially rescued normal bone marrow CD34+ cells and colony-forming cells from apoptosis induced by serum- and growth factor-deprivation. SDF-1 further enhanced cell survival, in synergy with IFN-γ. Short-term IFN-γ treatment of CD34+ cells enhanced the clonal growth of the cells in synergy with SDF-1. In contrast, IFN-γ inhibited the clonal growth of hematopoietic progenitor cells in a standard methylcellulose clonogenic assay and inhibited the growth factor-mediated survival of normal CD34+ cells, CD34+ cells from patients with chronic myeloid leukaemia, and MO7e cells. The addition of SDF-1 did not alter these outcomes. IFN-γ did not activate PI3K/Akt, enhance SDF-1-induced activation of PI3K/Akt, or up-regulate the expression of CXCR4 or its chemotactic function in bone marrow CD34+ cells. IFN-γ up-regulated the expression of Socs1 mRNA in CD34+ cells and MO7e cells. Referring to a previous report describing that Socs1 binds to multiple signalling proteins and suppresses stem cell factor-dependent proliferation of bone marrow-derived mast cells (De Sepulveda et al, EMBO J 18: 904,1999), it is suggested that IFN-γ-induced inhibition of the growth factor-dependent survival of CD34+ cells might be mediated, at least in part, through the induction of Socs1. Paradoxically, IFN-γ down-regulated SDF-1 production in primary human bone marrow stromal cells. These results indicate that IFN-γ, partly in concert with SDF-1, exerts dual effects on the survival and growth of hematopoietic progenitor cells; the effects of IFN-γ on hematopoietic progenitor cells can differ depending on the particular in vitro experimental conditions, especially the presence of hematopoietic growth factors.

The Contribution of Bone Marrow Stromal Cells to Leukemia Evolution: Differential Support of Leukemia Cell Growth at Diagnosis and Remission

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5419-5419
Author(s):  
Shlomit Yehudai-Reshef ◽  
Shira Attias ◽  
Tal Gabay ◽  
Rawan Sabah ◽  
Yael Morgenstern ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Cell Growth ◽  
Progenitor Cells ◽  
Stromal Cells ◽  
Leukemic Cell ◽  
Leukemic Cells ◽  
Hematopoietic Progenitor ◽  
Preferential Growth ◽  
Disease Stages

Abstract Introduction: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of the hematopoietic progenitor cells characterized by excessive proliferation of early progenitor cells in the bone marrow (BM) and is hence associated with a variable prognosis. BM niches are specialized types of microenvironment that actively support the growth, maturation and maintenance of hematopoietic stem and progenitor cells. They include a complex network of extracellular matrix proteins, soluble growth factors, and cytokines. Little is known about the leukemic microenvironment or its clinical relevance to AML initiation and propagation. The aim of the study was to define the role of stromal cells in support of leukemic cell growth in active disease as compared to the remission (Rm) state and normal stoma. Thus, we have investigated the expression of various cytokines secreted by stromal cells and involved in hematopoietic progenitor maintenance and proliferation at disease diagnosis (Dx) and Rm. Additionally, we have characterized the growth pattern of leukemic cells on various stroma cells from different sources and disease stages. Methods: Leukemic and stromal cells from BM of 4 patients with AML were collected at Dx. Stromal cells were also collected in Rm. Leukemic cells were enriched for CD34+ using magnetic beads. Patients' own stroma (POS) obtained both at Dx and Rm and the HS-5 cell line (control) were seeded on gelatin-treated plates and were grown with MesenCult medium for 42 days. Morphologic and growth rate changes were monitored every week using inverted microscopy X20. Upon adherence of 40-50% of the stromal cells, CD34+ enriched leukemic cells derived at Dx were seeded on top of POS from both Dx and Rm and were grown together for additional 2 weeks. Co-cultures were harvested and RNA was extracted followed by RT-PCR to amplify the following hematopoietic regulating genes: hepatocyte growth factor (HGF), fibroblast growth factor (FGF) and CXCL12. The results were expressed as arbitrary units normalized to GAPDH gene expression. Results: Expression of CXCL12 and HGF was elevated in a co-culture of leukemic cells and POS obtained at Dx compared to POS from Rm in all 4 patients. Additionally, the co-culture of leukemic cells and POS from Rm showed a higher expression of CXCL12 and HGF as compared to POS alone derived in Rm (Fig. 1). Mean values of cytokine expression were 37.33, 26.44 and 38.62 at Dx and 29.83, 25.55 and 24.55 in Rm for HGF, FGF and CXCL12, respectively. Additionally, a preferential growth advantage of colonies derived from single leukemic cells was observed when these cells were seeded on POS from Dx and relapse (Rx) compared to Rm (Fig. 2A). Moreover, colonies grew mainly in a co-culture with POS while no growth was noted on healthy stromal cells or stroma derived from a patient with myeloma (Fig. 2A) or another AML patient (Fig. 2B). Conclusions: Co-culture of AML cells and POS derived at Dx show a higher expression of CXCL12 and HGF compared to POS obtained in Rm, suggesting favorable microenvironment conditions supporting AML initiation and maintenance. A synergistic effect on expression of CXCL12 and HGF was observed in a co-culture of POS with leukemic cells as compared to POS or cell-line alone. Leukemic cells show preferential growth on POS and no growth on various malignant and normal stromal cells. Leukemic cell growth was diminished in Rm compared to Dx and Rx. Studying a larger number of patients as well as investigating the specific interaction of AML cells with stromal cells derived from various disease stages is needed to confirm the above results. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.

scholarly journals Polymorphic and monomorphic HLA-DR determinants on human hematopoietic progenitor cells

Blood ◽  
1984 ◽  
Vol 63 (5) ◽  
pp. 1125-1132 ◽  
Author(s):  
JH Falkenburg ◽  
J Jansen ◽  
N van der Vaart-Duinkerken ◽  
WF Veenhof ◽  
J Blotkamp ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Cell Sorting ◽  
Autologous Bone Marrow Transplantation ◽  
Autologous Bone Marrow ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Hla Dr ◽  
Complement Dependent Cytotoxicity ◽  
Class Ii Antigen

Abstract The expression of monomorphic Ia-like antigens and polymorphic (allotypic) HLA-DR determinants on CFU-GM, BFU-E, CFU-E, and CFU-GEMM was studied in bone marrow and peripheral blood cells from normal healthy individuals. Using various polyclonal and monoclonal anti-Ia- like antibodies, the presence of HLA-DR backbone antigens was shown on all hematopoietic progenitor cells (HPC) studied, both in complement- dependent cytotoxicity assays and in fluorescence-activated cell sorting (FACS). The expression of allotypic determinants was demonstrated on all HPCs, using the HLA-DR typing sera anti-HLA-DR1, 2, 3, 4, 5, and 7. The Class II antigen MT-2 was also shown on all HPCs, using both monoclonal and alloantisera, whereas the MB-1 (DC-1) determinant could not be demonstrated on HPCs. This might open the possibility of removing MB-1-positive malignant cells from the graft in autologous bone marrow transplantation.

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